Journal ArticleDOI
Molecular enzymology of the glyoxalase system.
TLDR
The glyoxalase system catalyzes the conversion of 2-oxoaldehydes into the corresponding 2-hydroxyacids and zinc plays an essential role in their diverse catalytic mechanisms.Abstract:
The glyoxalase system catalyzes the conversion of 2-oxoaldehydes into the corresponding 2-hydroxyacids. This biotransformation involves two separate enzymes, glyoxalase I and glyoxalase II, which bring about two consecutive reactions involving the thiol-containing tripeptide glutathione as a cofactor. The physiologically most important substrate methylglyoxal is converted by glyoxalase I into S-D-lactoyl-glutathione in the first reaction. Subsequently, glyoxalase II catalyzes the hydrolysis of this thiolester into D-lactic acid and free glutathione. The structures of both enzymes have been obtained via molecular cloning, heterologous expression, and X-ray diffraction analysis. Glyoxalase I and glyoxalase II are metalloenzymes and zinc plays an essential role in their diverse catalytic mechanisms. Both enzymes appear linked to a variety of pathological conditions, but further investigations are required to clarify the different physiological aspects of the glyoxalase system.read more
Citations
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Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): An overview of their mechanisms of formation
TL;DR: The aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.
Journal ArticleDOI
AGEs, RAGE, and Diabetic Retinopathy
TL;DR: The multiple components of the AGE-RAGE axis, including signal transduction, formation of ligands, and the end-point effectors, may be promising targets for strategies to treat diabetic retinopathy.
Journal ArticleDOI
The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach
TL;DR: Several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors are discussed, including modulation of the AGE-RAGE axis is considered promising in the prevention of neurodegenerative diseases.
Journal ArticleDOI
Role of advanced glycation endproducts and glyoxalase I in diabetic peripheral sensory neuropathy
Megan M. Jack,Douglas E. Wright +1 more
TL;DR: A review discusses AGEs, GLO1, their role in diabetic neuropathy, and potential therapeutic targets of the AGE pathway.
Journal ArticleDOI
Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and advanced lipoxidation end products
Giancarlo Aldini,Giulio Vistoli,Milan Stefek,Niki Chondrogianni,Tilman Grune,Jolanta Sereikaite,Izabela Sadowska-Bartosz,Grzegorz Bartosz +7 more
TL;DR: The review discusses inhibitors of ALE and AGE formation, cross-link breakers, ALE/AGE elimination by enzymes and proteolytic systems, receptors for advanced glycation end products (RAGEs) and blockade of the ligand–RAGE axis.
References
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Journal ArticleDOI
Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification--a role in pathogenesis and antiproliferative chemotherapy.
TL;DR: The modification of nucleic acids and protein by methylglyoxal is a signal for their degradation and may have a role in the development of diabetic complications, atherosclerosis, the immune response in starvation, aging and oxidative stress.
Journal ArticleDOI
Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal.
Takashi Tsuruo,Mikihiko Naito,Akihiro Tomida,Naoya Fujita,Tetsuo Mashima,Hiroshi Sakamoto,Hiroshi Sakamoto,Naomi Haga +7 more
TL;DR: In this article, a review on molecular cancer therapeutics, including molecular mechanisms and therapeutic approaches, is presented, focusing on the areas of drug resistance, apoptosis and apoptosis resistance, and survival-signaling.
Journal ArticleDOI
Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications.
TL;DR: A comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methyl glyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methyl-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases as discussed by the authors.